1L BTC Phase II/III Gemcitabine Plus Cisplatin With or Without Bintrafusp alfa (M7824)

Phase 1

• Conditions: Biliary Tract Cancer; MedDRA version: 20.0Level: LLTClassification code 10028982Term: Neoplasm biliary tractSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10073077Term: Intrahepatic cholangiocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10074879Term: Extrahepatic cholangiocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10017614Term: Gallbladder cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10034442Term: Periampullary carcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10034443Term: Periampullary carcinoma non-resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10034445Term: Periampullary carcinoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-001992-35-DE
• Lead Sponsor: Merck Healthcare KGaA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-10-28
• Last Update Posted: 13 September 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 524

Inclusion Criteria

1. Patients aged = 18 years of age at the time of signing the informed consent.

2. Participants with histologically or cytologically confirmed locally advanced or metastatic BTC, including intrahepatic CCA, extrahepatic CCA, gallbladder cancer and ampulla of Vater’s cancer. The histological origin of ampullary carcinomas (intestinal, pancreaticobiliary, or other) will be collected.

3. Naïve to chemotherapy, immunotherapy, and interventional radiological treatment (transarterial chemo-embolization, transarterial embolization, transarterial infusion) for locally advanced or metastatic BTC. Participants whose disease has recurred = 6 months after completion of neoadjuvant or adjuvant treatments will be considered eligible.

4. Availability of tumor tissue (primary or metastatic) (fresh or archival biopsies) before the first administration of study intervention. Availability of tumor tissue is mandatory except for the safety run-in part. Brush cytology, and cell blocks are not acceptable. Tumor tissue (fresh or archival) must be suitable for biomarker assessment as described in the Laboratory Manual.

5. At least 1 measurable lesion according to RECIST 1.1. Participants in the safety run-in part do not require a measurable lesion at baseline.

6. ECOG PS of 0 or 1 at study entry and at Week 1, Day 1 prior to dosing.

7. Life expectancy of = 12 weeks, as judged by the Investigator.

8. Adequate hematological function defined by white blood cell count = 2.0 × 10^9/Lwith absolute neutrophil count = 1.5 × 10^9/L, lymphocyte count = 0.5 × 10^9/L, platelet count = 100 × 10^9/L, and hemoglobin (Hgb) = 9 g/dL (participants may have been transfused) at study entry and at Week 1 Day 1 prior to dosing. Previously transfused participants are allowed in the study with a stable Hgb of = 9 g/dL at the time of study entry.

9. Adequate hepatic function defined by a total bilirubin level = 1.5 × upper limit of normal (ULN), an aspartate aminotransferase level = 3.0 × ULN, and an alanine aminotransferase level = 3.0 × ULN. For participants with liver involvement, aspartate aminotransferase = 5.0 × ULN and alanine aminotransferase = 5.0 × ULN are acceptable.

10. Adequate renal function defined by an estimated creatinine clearance (CrCl) > 50 mL/min according to the Cockcroft-Gault formula or by measure of CrCl from 24-hour urine collection.
CrCl (mL/min) = (140-age) × weight (kg) / (72 × serum creatinine [Crjaffe])
If female, × 0.85
If creatinine is measured by the enzymatic method, add 0.2 and use as Crjaffe = 0.2 + Crenzyme.

11. Albumin = 2.8 g/dL.

12. Adequate coagulation function defined as prothrombin time or international normalized ratio = 1.5 × ULN unless the participant is receiving anticoagulant therapy.

13. Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive participants must be treated and on a stable dose of antivirals (e.g., entecavir, tenofovir, or lamivudine; adefovir or interferon is not allowed) at study entry and with planned monitoring and management including baseline HBV DNA quantity according to appropriate labeling guidance. Participants receiving active hepatitis C virus (HCV) therapy must be on a stable dose at study entry and with planned monitoring and management according to appropriate labeling guidance of approved antiviral.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 256
F.1.3

Exclusion Criteria

1. Previous and/or intercurrent cancers. With the exception of: curatively-treated cancers with no recurrence in > 3 years or early cancers treated with curative intent, including but not limited to cervical carcinoma in situ, superficial, noninvasive bladder cancer, basal cell carcinoma, squamous cell carcinoma in situ, or endoscopically resected gastrointestinal cancers limited in mucosal layer.
2. Rapid clinical deterioration not related to malignancy which, in the opinion of the Investigator, may predispose to inability to tolerate treatment or study procedures at study entry and at Week 1 Day 1 prior to dosing.
3. Participants with symptomatic central nervous system (CNS) metastases are excluded. Participants with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they are judged to have fully recovered from treatment.
4. Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant).
5. Significant acute or chronic infections including:
- Known history of positive test for HIV or known acquired immunodeficiency syndrome
- Active tuberculosis (presence of clinical symptoms, physical or radiographic findings of active tuberculosis).
- Uncontrolled biliary infection. Biliary tract obstruction should be released by stenting or percutaneous transhepatic biliary drainage (PTBD).
- Active bacterial, fungal or viral infection (with the exception of hepatitis B and hepatitis C) requiring systemic therapy at study entry and at Week 1 Day 1 prior to dosing.
6. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
- Participants with type 1 diabetes, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
- Participants requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses = 10 mg of prednisone or equivalent per day.
- Administration of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intra-ocular, or inhalation) is acceptable.
7. History of, or concurrent, interstitial lung disease.
8. Known history of hypersensitivity reactions to bintrafusp alfa or its products or known severe hypersensitivity reactions to monoclonal antibodies (Grade = 3 NCI-CTCAE] Version 5.0), any history of anaphylaxis, or recent (within 5 months) history of uncontrolled asthma.
9. Clinically significant cardiovascular/cerebrovascular disease as follows: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification = Class II), or serious cardiac arrhythmia.
10. Other severe, acute, or chronic medical conditions, including immune colitis, inflammatory bowel disease, immune pneumonitis, or psychiatric conditions, including recent (within the past year) or active suicidal ideation or behavior.
11. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before randomization.
12. Participants who are candidates for liver transplantation and who can receive the transpl

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified